Heat Shock Proteins and Mitogen-activated Protein Kinases in Steatotic Livers Undergoing Ischemia-Reperfusion: Some Answers

• Published in: The American journal of pathology Vol. 168; no. 5; pp. 1474 - 1485
• Main Authors: Massip-Salcedo, Marta, Casillas-Ramirez, Araní, Franco-Gou, Rosah, Bartrons, Ramón, Ben Mosbah, Ismail, Serafin, Anna, Roselló-Catafau, Joan, Peralta, Carmen
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2006; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Fatty Liver - metabolism; Heat-Shock Proteins - metabolism; Heme Oxygenase-1 - metabolism; Investigative techniques, diagnostic techniques (general aspects); Ischemic Preconditioning; Liver - blood supply; Liver - pathology; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; Nitric Oxide - physiology; Original Research Paper; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Protein Kinase C - metabolism; Rats; Rats, Zucker; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Time Factors; Anatomic pathology; Digestive system; Enzyme; Liver; Ischemia reperfusion; Heat shock protein; Mitogen-activated protein kinase
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2006.050645

Ischemic preconditioning protects steatotic livers against ischemia-reperfusion (I/R) injury, but just how this is achieved is poorly understood. Here, I/R or preconditioning plus I/R was induced in steatotic and nonsteatotic livers followed by investigating the effect of pharmacological treatments that modulate heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs). MAPKs, HSPs, protein kinase C, and transaminase levels were measured after reperfusion. We report that preconditioning increased HSP72 and heme-oxygenase-1 (HO-1) at 6 and 24 hours of reperfusion, respectively. Unlike nonsteatotic livers, steatotic livers benefited from HSP72 activators (geranylgeranylacetone) throughout reperfusion. This protection seemed attributable to HO-1 induction. In steatotic livers, preconditioning and geranylgeranylacetone treatment (which are responsible for HO-1 induction) increased protein kinase C activity. HO-1 activators (cobalt(III) protoporphyrin IX) protected both liver types. Preconditioning reduced p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in HSP72 induction though HO-1 remained unmodified. Like HSP72, both p38 and JNK appeared not to be crucial in preconditioning, and inhibitors of p38 (SB203580) and JNK (SP600125) were less effective against hepatic injury than HO-1 activators. These results provide new data regarding the mechanisms of preconditioning and may pave the way to the development of new pharmacological strategies in liver surgery.